Open Access Highly Accessed Research article

Testing the thrifty gene hypothesis: the Gly482Ser variant in PPARGC1A is associated with BMI in Tongans

Sean Myles123*, Rod A Lea4, Jun Ohashi5, Geoff K Chambers6, Joerg G Weiss3, Emilie Hardouin127, Johannes Engelken117, Donia P Macartney-Coxson4, David A Eccles6, Izumi Naka5, Ryosuke Kimura8, Tsukasa Inaoka9, Yasuhiro Matsumura10 and Mark Stoneking7

Author Affiliations

1 Institute for Genomic Diversity, Cornell University, Ithaca, NY, USA

2 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY, USA

3 Department of Biology, Acadia University, Wolfville, Canada

4 Institute of Environmental Science and Research Ltd, Porirua, New Zealand

5 Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan

6 School of Biological Sciences, Victoria University of Wellington, New Zealand

7 Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany

8 Transdisciplinary Research Organization for Subtropical and Island Studies (TRO-SIS), University of the Ryukyus, Okinawa, Japan

9 Department of Human Ecology, Faculty of Agriculture, Saga University, Saga, Japan

10 Faculty of Health Care, Kiryu University, Gunma, Japan

11 Institute of Evolutionary Biology, Pompeu Fabra University, Barcelona, Spain

12 Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Biology, Plön, Germany

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BMC Medical Genetics 2011, 12:10  doi:10.1186/1471-2350-12-10

Published: 18 January 2011

Abstract

Background

The thrifty gene hypothesis posits that, in populations that experienced periods of feast and famine, natural selection favoured individuals carrying thrifty alleles that promote the storage of fat and energy. Polynesians likely experienced long periods of cold stress and starvation during their settlement of the Pacific and today have high rates of obesity and type 2 diabetes (T2DM), possibly due to past positive selection for thrifty alleles. Alternatively, T2DM risk alleles may simply have drifted to high frequency in Polynesians. To identify thrifty alleles in Polynesians, we previously examined evidence of positive selection on T2DM-associated SNPs and identified a T2DM risk allele at unusually high frequency in Polynesians. We suggested that the risk allele of the Gly482Ser variant in the PPARGC1A gene was driven to high frequency in Polynesians by positive selection and therefore possibly represented a thrifty allele in the Pacific.

Methods

Here we examine whether PPARGC1A is a thrifty gene in Pacific populations by testing for an association between Gly482Ser genotypes and BMI in two Pacific populations (Maori and Tongans) and by evaluating the frequency of the risk allele of the Gly482Ser variant in a sample of worldwide populations.

Results

We find that the Gly482Ser variant is associated with BMI in Tongans but not in Maori. In a sample of 58 populations worldwide, we also show that the 482Ser risk allele reaches its highest frequency in the Pacific.

Conclusion

The association between Gly482Ser genotypes and BMI in Tongans together with the worldwide frequency distribution of the Gly482Ser risk allele suggests that PPARGC1A remains a candidate thrifty gene in Pacific populations.